Identification of GJB۲ Variants in ۷۵ Unrelated Iranian Autosomal Recessive Non-syndromic Hearing Loss Patients

Background: Hearing loss (HL) is the most prevalent sensory disease in humans. HL is among the most clinically and genetically heterogeneous disorders. Pathogenic variants in GJB۲ are the main cause of HL in manypopulations. Therefore, GJB۲ analysis should be considered as the first step for HL. Objectives: This study aimed to find causative variants in the GJB۲ gene in ۷۵ unrelated Iranian patients who suffered from Autosomal recessive non-syndromic hearing loss (ARNSHL). Methods: Peripheral blood samples were used for genomic DNA extraction. PCR-direct sequencing was performed to detect GJB۲ mutations. Results: In this study, thirty-four chromosomes (۲۱.۳۳%) carried GJB۲ mutations. In total, ۱۰ variants in ۱۹ cases were detected. Seven cases were homozygous for c.۳۵delG; (p.Gly۱۲Valfs*۲), two were homozygous for c.۷۱G>A; (p.Trp۲۴*), two were homozygous for c.۳۵۸-۳۶۰delGAG (p.Glu۱۲۰del), and two were homozygous for c.-۲۳+۱G>A mutations. One patient was a compound heterozygote for c.۳۵delG and c.-۲۳+۱G>A mutations, and another patient with compound heterozygosity for c.۲۹۰dupA and c.۲۳۵delC mutations were determined. Four patients carried a mono-allelic variant in the GJB۲ including c.۱۲۶G>T; (p.Glu۴۲Asp), c.۲۳C>T; (p.Thr۸Met), c.۴۴۵G>A; (p.Ala۱۴۹Thr) and c.۲۶۹T>C; (p.Leu۹۰Pro). Accordingly, c.۳۵delG mutation was the most common variant in this study. Conclusions: Finding common variants of HL mutations in different populations can elevate the diagnostic value of molecular testing in the screening of affected individuals, and can improve counselling to minimize the risk of having affected offspring for at-risk couples. Besides, early diagnosis can easily lead to speech development and prevents further problems.